The in vitro PIG-A gene mutation assay: mutagenicity testing via flow cytometry based on the glycosylphosphatidylinositol (GPI) status of TK6 cells.

The X-linked PIG-A gene is involved in the biosynthesis of the cell surface anchor GPI, and its inactivation may serve as a new marker for mutagenicity. The in vivo PIG-A gene mutation assay is currently being validated by several groups. In this study, we established a corresponding in vitro variant of the PIG-A assay applying B-lymphoblastoid TK6 cells. PE-conjugated antibodies against the GPI-anchored proteins CD55 and CD59 were used to determine the GPI status via multicolor flow cytometry. Mutant spiked TK6 cell samples were analyzed, and mutants were quantified with even small numbers being quantitatively recovered. To validate our approach, mutant spiked cell samples were analyzed by flow cytometry and proaerolysin selection in parallel, yielding a high correlation. Further, we developed a procedure to reduce the background level of preexisting mutant cells to lower than 20 in 10(6) cells to increase the sensitivity of the assay. Spontaneous rate of GPI deficiency was investigated being 0.76 × 10(-6)/cell/generation for TK6 cells. The optimal phenotype expression time after ethyl methanesulfonate treatment was found to be 10 days. We applied the in vitro PIG-A assay to demonstrate the mutagenicity of ethyl methanesulfonate, 4-nitroquinoline 1-oxide and UV-C irradiation in a dose-dependent and statistically significant manner. Pyridine and cycloheximide were included as negative controls providing negative test results up to 10 mM. These data suggest that the in vitro PIG-A assay could complement the in vivo PIG-A assay with some distinct advantages compared to other in vitro mammalian mutagenicity tests.

The course of PTSD in naturalistic long-term studies: high variability of outcomes. A systematic review.

BACKGROUND: With a lifetime prevalence of 8% posttraumatic stress disorder (PTSD) is one of the most common mental disorders; nevertheless, its longitudinal course is largely unknown. AIMS: Our aim was to conduct a systematic review summarizing available findings on the prospective, naturalistic long-term course of PTSD and its predictors. METHODS: Databases MEDLINE and PsycINFO were searched. Main selection criteria were: 1) naturalistic cohort study with a follow-up period of at least 3 years, 2) adult participants with observer-rated or probable PTSD at baseline. RESULTS: Twenty-four cohorts (25 studies) were retrieved (14 with observer-assessed, 10 with probable PTSD). In total, they comprised about 10,500 participants with PTSD at baseline that were included in the long-term follow-ups. Studies investigating patient populations with observer-assessed PTSD found that between 18% and 50% of patients experienced a stable recovery within 3-7 years; the remaining subjects either facing a recurrent or a more chronic course. Outcomes of community studies and studies investigating probable PTSD varied considerably (remission rates 6-92%). Social factors (e.g. support) as well as comorbid physical or mental health problems seem to be salient predictors of PTSD long-term course and special focus should be laid on these factors in clinical settings. CONCLUSIONS: Included studies differed notably with regard to applied methodologies. The resulting large variability of findings is discussed. More standardized systematic follow-up research and more uniformed criteria for remission and chronicity are needed to gain a better insight into the long-term course of PTSD.

The relationship between skill deficits and disability-a transdiagnostic study.

OBJECTIVE: Transdiagnostic skills (e.g., emotion regulation, stress management) and related self-concepts (e.g., self-esteem) are associated with the pathogenesis and course of different mental disorders. Evidence suggests that skill deficits coincide with not only specific psychopathology but also psychological strain and disability. So far, studies examining the relevance of several skills for a patient's disability are lacking. The aim of the present study was the combined assessment of 7 skills and self-concept variables to simultaneously analyze their relevance for disability. METHOD: We interviewed inpatients (N = 183) both on admission and discharge to assess 7 specific skills, 7 areas of daily living disability, and psychopathological distress. RESULTS: Results support a relationship between several skills and disability (especially stress management), even while controlling for psychopathology. The improvement of skills and related self-concepts during therapy contributed substantially to the improvement of disability ratings. CONCLUSION: This study highlights the transdiagnostic importance of skills as well as the improvement of skills and related self-concepts as major determinants of disability. Parts of these effects are robust, even while controlling for psychopathology.

[Evaluation of medical and psychological expert opinions in asylum and residence legislation]. / Evaluation ärztlicher und psychologischer Bescheinigungen in asyl- und aufenthaltsrechtlichen Verfahren.

The quality of medical and psychological certificates and expert opinions in asylum and residence legislation was analyzed using judicial requirements as well as standards of the German Bundesärztekammer (SBPM). A sample of 53 cases of asylum seekers including 86 medical certificates and 15 expert opinions was evaluated qualitative and quantitative. The quality varies strongly from exemplary to insufficient. Predominantly, the medical certificates did not comply with judicial requirements. Two thirds of the expert opinions met the standards formulated by SBPM. Experts should write medical/psychological opinions being familiar with both traumatized individuals and refugees. The minimum requirements and standards should be better communicated to involved medical and psychological practitioners.

[Psychosomatic and psychotherapeutic outpatient care in Germany - Capacity profile based on data from the National Association of Statutory Health Insurance Physicians]. / Ambulante psychosomatische und psychotherapeutische Versorgung in Deutschland - Versorgungsprofile abgebildet durch Daten der Kassenärztlichen Bundesvereingung (KBV).

OBJECTIVES: At the centre of the study lay a representation of outpatient psychosomatic and psychotherapeutic care with a focus on different groups of medical and psychological therapists. METHODS: The routine data of the National Association of Statutory Health Insurance Physicians (KBV) from the year 2008 were analyzed based on a systematic literature review (Medline, ISI, to November 2010). RESULTS: Neurologists and psychiatrists see the most patients (n = 3,172 vs n = 1,347 cases per practice), but they rarely provide services according to the directives for psychotherapy (4,4 %). However, specialists for psychosomatic medicine and psychotherapy (65 %), physicians providing only psychotherapy (66 %) and psychological psychotherapists (73 %) provide care mainly according to the directives for psychotherapy and therefore see fewer patients (170-190 cases per practice).Medical psychotherapists work more often on a psychodynamic basis, while psychological psychotherapists perform more often behavioral therapy. CONCLUSIONS: The treatment of patients with mental and psychosomatic disorders is based on three columns of care, which differ in their supply profile and each make a specific contribution to the treatment.

Expectations, end-of-life fears and end-of-life communication among palliative patients with cancer and caregivers: a cross-sectional study.

OBJECTIVES: During serious illness, open communication with caregivers can ensure high-quality care. Without end-of-life communication, caregivers may become surrogates and decision-makers without knowing the patient's preferences. However, expectations and fears may influence the initiation of communication. The present study investigates differences between palliative patients with cancer and caregivers regarding expectations of end-of-life communication, end-of-life fears and experiences with end-of-life communication. DESIGN: A cross-sectional study using a semi-structured interview and a paper-based questionnaire SETTING: University Hospital in Germany. PARTICIPANTS: 151 participants: 85 palliative cancer patients (mean age: 62.8 years, 65.9% male) and 66 caregivers (mean age: 56.3 years, 28.8% male). PRIMARY AND SECONDARY OUTCOME MEASURES: Expectations, end-of-life fears and experiences of end-of-life discussions. RESULTS: Patients and caregivers wish for the patient to be self-determined. In general, participants reported more positive than negative expectations of end-of-life discussions. Importantly, concerns about emotionally burdening other person was rated much higher in an informal context than a professional context (F(1,149)=316 958, p<0.001, ηp²=0.680), even though the emotional relief was expected to be higher (F(1,149)=46.115, p<0.001, ηp²=0.236). Caregivers reported more fears about the last period of life and more fears about end-of-life discussions than palliative patients, whereas palliative patients tended to avoid the topics of death and dying to a greater extent. CONCLUSIONS: There seems to exist a 'self-other' asymmetry: palliative patients and their caregivers expect substantial personal relief when openly talking about end-of-life issues, but also expect the other person to be burdened by such communication. Professionals repeatedly need to initiate end-of-life communication.

Assessing patients´ preferences for breaking Bad News according to the SPIKES-Protocol: the MABBAN scale.

OBJECTIVE: Quality of breaking bad news can seriously affect the course of disease. A frequently applied guideline is the SPIKES-Protocol that have been designed from the physician's perspective. Little is known about patients' preferences in breaking bad news. Our aim was to develop a questionnaire based on the SPIKES-protocol to detect patients´ preferences for breaking bad news communication. METHODS: TheMarburg Breaking Bad News Scale (MABBAN) was developed and administered to 336 cancer patients. We used exploratory factor analysis. To examine potential relationships according to demographic and medical variables, regression analyses were conducted. RESULTS: The novel questionnaire supported the six SPIKES-components of breaking bad news: Setting, Perception, Invitation, Knowledge, Emotions, and Strategy. Perception and Invitation clustered together to one subscale. Depending on clinical and demographic variables different components were rated as important. CONCLUSION: Communication preferences in breaking bad news can be assessed using a SPIKES-based questionnaire. Physicians should improve the setting, share knowledge in all clarity, involve the patients in further planning, and consider demographical variables. PRACTICE IMPLICATIONS: Using SPIKES as a framework can optimize breaking bad news conversations but it seems important to emphasize the individual preferences beyond the six steps and tailor the communication process to the individual.

The prospective long-term course of adult depression in general practice and the community. A systematic literature review.

BACKGROUND: Findings about the prospective long-term course of depression are usually derived from clinical populations while knowledge about the course in community and primary care samples is rarer. As depressive disorders are highly prevalent and associated with considerable disability and costs, this information is needed to identify the percentages of subjects with a favorable or unfavorable prognosis. Therefore our aim was to summarize the available evidence on the prospective longitudinal course of depression in both general practice and the community. METHODS: We conducted a systematic, computerized search of Medline and PsycINFO. Main selection criteria were (a) adults with observer assessed depressive disorder recruited in the community or in general practice and (b) naturalistic study with follow-up length of at least three years. As primary outcome the percentages of stable recovery, recovery during or at follow-up, recurrence and chronic course were used. RESULTS: We identified 12 cohorts, with 4009 followed-up individuals. Follow-up intervals ranged between three and 49 years. Between 35% and 60% of participants experienced a stable recovery with no (further) recurrences, while 70-85% recovered at least once during follow-up. A consistent percentage of 10-17% had a chronic course. Recurrence rates varied considerably ranging between 7% and 65%. Significant predictors of an unfavorable course appear to be mainly those variables that lie within the course of depression itself, i.e. history of depression, baseline severity, and comorbidity. LIMITATIONS: Use of broad inclusion criteria heightened study heterogeneity and hampered comparability. CONCLUSION: Regarding stable recovery, the long-term course within general practice and community samples seems more favorable than within clinical samples. Further research applying a standardized methodology is required.

Relapse rates after psychotherapy for depression - stable long-term effects? A meta-analysis.

BACKGROUND: Depression is the most common mental disorder. Effective psychotherapeutic treatments for depression exist; however, data on their long-term effectiveness beyond a time span of two years is still scarce. Our aim was to perform a meta-analysis, investigating (a) overall rates of relapse more than two years after psychotherapy (meta-analysis 1), and (b) if psychotherapy has more enduring effects than non-psychotherapeutic comparison conditions (e.g. pharmacotherapy, treatment as usual), again beyond a time span of two years post-therapy (meta-analysis 2). METHODS: We searched electronic databases Medline, PsycINFO and the COCHRANE Library. Main selection criteria were (i) RCT of psychotherapy with follow-up interval of more than 2 years, (ii) primary diagnosis of depression, assessed by observer ratings, (iii) report of relapse at follow-up. RESULTS: We identified 11 studies, 6 of which included a non-psychotherapeutic comparison condition. Together they comprised long-term data of 966 patients. Mean follow-up duration was 4.4 years. The overall relapse rate at long-term follow-up was 0.39 (95% CI 0.29, 0.50). Psychotherapy resulted in significantly less relapses (53.1% vs. 71.1%, OR 0.51; 95% CI 0.32, 0.82, p=0.005) than comparison treatments. This finding corresponded to a number needed to treat (NNT) of 5.55. LIMITATIONS: Results can only be preliminary as data was sparse and studies differed methodologically. Heterogeneity in the first meta-analysis was high (I(2)=82%). Results indicated publication bias. CONCLUSIONS: The relapse rate more than two years after psychotherapy is relatively high, but significantly lower compared to non-psychotherapeutic treatments. Multiannual follow-ups should routinely be included in future psychotherapy RCTs.

Depression as a risk factor for mortality in individuals with diabetes: a meta-analysis of prospective studies.

OBJECTIVE: To quantify the impact of depression measured by self-reports and depression measured by clinical interview on all-cause mortality in individuals with diabetes and to analyze the strength of both associations, the influence of covariates, and possible differences between studies assessing self-rated depressive symptoms and those using a clinical interview to measure depression as predictors of mortality. RESEARCH DESIGN AND METHODS: PUBMED and PsycINFO were searched up to July 2013 for prospective studies assessing depression, diabetes and mortality. The pooled hazard ratios were calculated using random-effects models. RESULTS: Sixteen studies met the inclusion criteria. After adjustment for demographic variables depression measured by self-reports was associated with an increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89-3.47), and the mortality risk remained high after additional adjustment for diabetes complications (HR = 1.76, 95% CI 1.45-2.14,). Six studies reporting adjusted HRs for depression measured by clinical interviews supported the results of the other models (HR = 1.49, 95% CI 1.15-1.93). CONCLUSIONS: Both depression measured by self-report and depression measured by clinical interview have an unfavorable impact on mortality in individuals with diabetes. The results, however, are limited by the heterogeneity of the primary studies. It remains unclear whether self-reports or clinical interviews for depression are the more precise predictor.

What do we know today about the prospective long-term course of social anxiety disorder? A systematic literature review.

While we know that social anxiety disorder (SAD) is today's most common anxiety disorder knowledge on its prospective long-term course is sparse. We conducted a systematic literature search using databases Medline and PsycINFO for naturalistic and psychotherapy outcome studies with follow-up durations of at least 24 months. Four naturalistic cohorts and nine psychotherapy trials were included in the review. The naturalistic course in clinical was less favorable than in non-clinical samples (27% vs. 40% recovery rate after 5 years). Psychotherapy trials, all applying (cognitive) behavioral methods, yielded stable outcomes with overall large pre- to follow-up effect sizes on self-report scales. Observer rated remission rates varied considerably (36% to 100%) depending on study design and follow-up length. The results of psychotherapy trials and that of naturalistic studies can hardly be compared due to differences in methodology. More standardized remission and recovery criteria are needed to enhance the understanding of the longitudinal course.

What determines observer-rated social performance in individuals with social anxiety disorder?

Clark and Wells (1995) proposed that cognitive variables and safety behaviors are related to social performance in social anxiety disorder (SAD). Here, we tested this relationship by concurrent assessment of cognitive, behavioral, and physiological variables and social performance in a prototypical social interaction situation. 103 participants with SAD and 23 healthy controls interacted with a confederate. Anxiety, self-focused attention, cognitions, and safety behaviors were assessed by self-report and by confederate ratings. Social performance was evaluated by independent observers using a behavioral coding system. Social performance was predicted using two regression models for self-report and confederate ratings. Between-group differences in social performance disappeared when talking time was taken into account. Talking time emerged as the most powerful predictor of social performance (54% and 58% accounted variance). Positive cognitions, self-focused attention and safety behaviors accounted for an additional, but marginal amount of variance. Reduced talking time might represent a safety behavior and may be considered an easy to measure final common behavioral outcome of cognitive processes underlying social anxiety.